Mohamed Zaghloul, MD, MSc, MBBCh, of Cairo University in Egypt, and his colleagues compared LRFS between those who received adjuvant sandwich chemotherapy plus RT and adjuvant chemotherapy alone in a phase 2 extension of a phase 3 randomized trial of 120 Egyptian patients (aged 70 years and younger) with mostly pT3 and higher disease. More than half (53%) had urothelial carcinoma (UC), and 46.7% had squamous cell carcinoma or other histology. After radical cystectomy (RC) with standard lymph node dissection, all patients had negative surgical margins with risk factors for recurrence (i.e., higher than pT3b, grade 3, or positive lymph nodes).

The 75 patients in the chemotherapy plus RT arm received 2 cycles of gemcitabine (1000 mg/m2 intravenously [IV] on days 1, 8, and 15) and cisplatin (70 mg/m2 IV on day 2) before and after RT to 4500 cGy (in 150 cGy twice-daily fractions over 3 weeks) using 3-D conformal techniques. The chemotherapy alone arm, including 45 patients, received 4 cycles of gemcitabine and cisplatin.

“Adjuvant chemotherapy plus RT was reasonably well tolerated and was associated with significant improvements in LRFS and marginal improvements in disease-free survival vs chemotherapy alone in LABC,” Dr Zaghloul and his colleagues stated. “The addition of adjuvant RT should be considered for LABC. This regimen warrants further study in phase 3 trials.”

The writers of an accompanying editorial were more skeptical. “Although provocative, the study by Zaghloul and colleagues has some important limitations,” Dayssy A. Diaz, MD, Amir Mortazavi, MD, and Cheryl T. Lee, MD, of Ohio State University commented. They highlighted imbalances between treatment arms, such as differences in age, tumor size, and the number of resected lymph nodes.

“Ultimately, should ART be considered in patients with locally advanced UC after cystectomy? In an era of cisplatin-based neoadjuvant chemotherapy (NAC), it is uncertain how this regimen would be integrated into accepted treatment paradigms because NAC was not part of the trial design by Zaghloul and colleagues,” the editorial writers observed.

Still, patients with at least pT3 disease following NAC have a significant risk of local recurrence, they noted. Further, current guidelines from the National Comprehensive Cancer Network support consideration of ART in patients with high-risk UC following RC.